Regional enteritis (RE) and gluten sensitive enteropathy (GSE) (celiac sprue) share in common the posssibility that immunologic factors may play a major role in their pathogenesis. The advent of organ culture methods capable of maintaining intestinal biopsies viable for 24 to 48 hours affords the opportunity to study these diseases in fashion that will lend insight into the basic disease processes. Initially, by means of isotopic labelling, using short-term incubation methods, we will define small intestinal protein, immunoglobulin, and DNA synthesis in biopsy specimens from patients with RE and GSE. In addition, brush border enzyme activities (alkaline phosphatase, sucrase, lactase, and trehalase) will be measured. The findings will be correlated with the microscopic morphology of the tissue. These parameters will be studied in longer-term organ culture of tissue specimens from patients with GSE. The effect of added gluten or gluten fractions to the culture media on rates of protein, immunoglobulin, and DNA synthesis, as well as brush border enzyme activity and tissue morphology will be studied in an attempt to define the toxic moiety of gluten. Using affinity chromatography, we will characterize the antigluten antibodies made by tissue in culture. The antibody will be isolated and purified, and it will be used in an attempt to reproduce the intestinal lesion in vitro, thus helping to prove that an immunologic response may be responsible for the lesion of GSE. The effects of serum immunoglobulins, blood lymphocytes, cortisone, and duodenal juices from patients with GSE and controls on protein, immunoglobulin and DNA synthesis, brush border enzymes and morphology of cultured tissue specimens will also be examined. In RE, the effects of anti-inflammatory agents such as cortisone, azathioprine, and azulfidine on the above parameters will be examined. It is hoped that these studies may lead to the development of in vitro models of these diseases which will yield insight into their pathogenesis and suggest new modes of therapy.